DBI-1, a novel gene related to the notch family, modulates mitogenic response to insulin-like growth factor 1.
The insulin-like growth factor 1 (IGF-1) receptor has been found to transform fibroblast cells when overexpressed. The removal of 108 aa from the C-terminus of the IGF-1 receptor abolishes the transforming ability of the receptor without affecting its ability to induce cell growth. The availability of this mutant receptor provides a means to examine the changes in gene expression which take place during transformation, solely in response to an increased number of IGF-1 receptors. Using differential display, we have examined differences in gene expression between cells expressing a wild-type, transforming IGF-1 receptor and cells expressing a C-terminally truncated, nontransforming IGF-1 receptor. We have cloned a novel 6. 3-kb cDNA transcript (DBI-1) which is expressed at much lower levels in cells containing the wild-type IGF-1 receptor. The predicted protein sequence of DBI-1 contains seven EGF-like repeats, which bear >90% sequence identity to the rat Notch 2 protein. The cDNA also contains a potential DEAD box in the C-terminal region. The DBI-1 message is detected at relatively high levels in cardiac tissue and at lower levels in lung, liver, and kidney. Antibodies generated to a unique region of the DBI-1 protein recognize a protein of 88 kDa, which is localized in the nucleus. Overexpression of DBI-1 in cells which contain the wild-type IGF-1 receptor diminishes the mitogenic response to IGF-1.
Hoff
H B
HB
Department of Pathology and Laboratory Medicine, MCP-Hahnemann School of Medicine, Allegheny University, 2900 Queen Lane, Philadelphia, Pennsylvania 19129, USA.
Tresini
M
M
Li
S
S
Sell
C
C
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D003001:Cloning, Molecular; D053487:DEAD-box RNA Helicases; D004247:DNA / Q000096:biosynthesis; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D005796:Genes / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D025521:Tumor Suppressor Proteins
D018076:DNA, Complementary; C110734:Ints6 protein, mouse; D008934:Mitogens; C497765:Notch2 protein, mouse; C497766:Notch2 protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D007334:Insulin-Like Growth Factor I; D004247:DNA; D017526:Receptor, IGF Type 1; D053487:DEAD-box RNA Helicases